C-X-C chemokine receptor type 7 (CXCR7)

C-X-C chemokine receptor type 7 (CXCR7), also known as atypical chemokine receptor 3 (ACKR3) or RDC1, is a member of the G protein-coupled receptor superfamily, structurally characterized by seven transmembrane domains. Unlike typical chemokine receptors, CXCR7 primarily signals through beta-arrestin pathways rather than G proteins, making it an atypical chemokine receptor. It binds chemokines such as stromal cell-derived factor 1 (CXCL12/SDF-1) and interferon-inducible T-cell alpha chemoattractant (CXCL11/I-TAC) with high affinity, functioning as a scavenger receptor that tightly regulates chemokine concentrations in the microenvironment. CXCR7 is expressed in various tumor and endothelial cells as well as in certain normal tissues. It is involved in cell proliferation, survival, adhesion, angiogenesis, and modulation of the immune response. Upregulation of CXCR7 is frequently implicated in tumorigenesis, metastatic spread, and resistance to therapeutic modalities, making it a significant emerging target for anticancer drug development. Drugs targeting CXCR7 are being developed, mostly as small molecule antagonists, for use in cancer and inflammatory diseases. Its complex interactions with CXCR4 and its chemokine ligands present both therapeutic opportunities and challenges.

Other names

ACKR3RDC1Atypical chemokine receptor 3GPR159Chemokine (C-X-C motif) receptor 7CXC chemokine receptor 7

Antagonists/ligand blockers inhibit receptor-ligand binding and downstream beta-arrestin signaling, leading to decreased tumor proliferation, angiogenesis, and metastasis. Agonists or biased ligands can modulate beta-arrestin recruitment, leading to altered signal transduction and receptor trafficking.